Melanoma
Conditions
Keywords
melanoma, ipilimumab, coxsackievirus A21, CAVATAK, CVA21, checkpoint inhibitors
Brief summary
Open label, single arm study of intratumoral CVA21 and ipilimumab in advanced melanoma patients.
Detailed description
Primary Objective: To evaluate the safety and efficacy of CAVATAK (CVA21) administered intratumorally in combination with the approved dose and schedule of ipilimumab. Of particular interest is to estimate the overall response rate (ORR) in the subgroup of subjects with unresectable or metastatic stage III B/C or IV melanoma who have progressed on a single prior anti-PD-1 therapy. Secondary Objectives: 1. Assess the clinical efficacy of ipilimumab in combination with intratumoral CVA21 in terms of: * Immune-related progression-free survival (irPFS) at 6 and 12 months, * Durable response rate (DRR), * 1-year survival, * Overall survival (OS), and * Quality of life. 2. Assess the response of injected and non-injected melanoma lesions after CVA21 and ipilimumab. 3. Assess the time to initial response.
Interventions
BIOLOGICALCAVATAK
CAVATAK is a preparation of CVA21
DRUGIpilimumab
Ipilimumab is a human cytotoxic T-lymphocyte antigen (CTLA-4)-blocking antibody indicated for the treatment of unresectable or metastatic melanoma
Sponsors
Providence Health & Services
Viralytics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with unresectable or metastatic stage III B/C or IV melanoma. Patients enrolled under this version of the protocol must also have progressed on prior anti-PD-1 therapy, according to RECIST 1.1 criteria. Patients who progressed within 3 months of treatment start are excluded. 2. Patients must have at least one cutaneous or subcutaneous tumor, measuring 0.5 to 5.0 cm in the longest diameter, or a palpable lymph node. At least one tumor must qualify as an index lesion that can be accurately and reproducibly measured in two dimensions for which the longest diameter is .10 mm (.15 mm in short axis diameter \[SAD\] for lymph nodes), and be amenable to intratumoral injection. 3. Histological confirmation of melanoma will be required by previous biopsy or cytology. 4. Patients who have received prior ipilimumab treatment for metastatic melanoma are not eligible. 5. Patients with ≤ 3 visceral metastases (excluding pulmonary lesions), with no lesions \>3.0 cm. Patients with substantial tumor burden of non-measurable disease may not be good candidates for an immunotherapy and should be discussed with the Medical Monitor. 7\. ECOG performance status of 0-1. Key
Exclusion criteria
1. Patients with tumors to be injected lying close to an airway, major blood vessel or spinal cord that, in the opinion of the Investigator, could cause occlusion or compression in the case of tumor swelling or erosion into a major vessel in the case of necrosis. Patients with lesions in mucosal areas (vulvar, anus, oral cavity, etc.), are eligible, as long as the subject has at least one lesion suitable for injection; consult Medical Monitor for confirmation. 2. Patients with active, known or suspected autoimmune disease except for autoimmune thyroiditis or vitiligo. Thyroiditis patients must be asymptomatic, on adequate thyroid replacement and have normal thyroid function tests. 3. Patients with active colitis or immune-mediated colitis that has not resolved to grade 1 or less. 4. Patients with untreated brain metastases. Patients with treated brain metastases who are off corticosteroids for at least two weeks and who demonstrate control of brain metastases with follow-up imaging 4 or more weeks after initial therapy are eligible. 5. Patients previously treated with CVA21.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response | 106 days | Best response of complete response (CR) or partial response (PR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DRR | lasting 26 weeks or longer | Durable Response Rate |
| PFS | At 6 and 12 months | Progression-Free Survival |
| OS | Through study completion, an average of 2 years | Overall |
Countries
United States
Outcome results
None listed